RESEARCH Antibiotics Aplenty T h e r a p y for antibiotic-resistant diseases, as w e l l as fungus diseases, p r o m i s e d b y n e w antibiotics SEVERAL
NEW
ANTIBIOTICS
were
un-
v e i l e d in W a s h i n g t o n l a s t w e e k b e f o r e t h e third a n n u a l S y m p o s i u m on Anti biotics s p o n s o r e d by the F o o d a n d D r u g Administration. O n h a n d to d i s p l a y t h e i r a n t i b i o t i c s w a r e s w e r e m o s t of t h e m a j o r d r u g c o m p a n i e s . S e v e r a l offered n e w materials produced b y Strepto myces t h a t a t t a c k t h e old b u g a b o o d e v e l o p m e n t of r e s i s t a n c e , p a r t i c u l a r l y by gram positive bacteria. ψ- C a T n o m y c ï n , say îvîeruk Scientists, is u n i q u e i n t h a t it is effective a g a i n s t bacteria ( particularly staphylococci ) r e s i s t a n t t o k n o w n a n t i b i o t i c s , it is e q u a l l y effective orally or b y injection, a n d h i g h c o n c e n t r a t i o n s r e m a i n in t h e b l o o d for l o n g periods c o m p a r e d w i t h other antibiotics. I n test t u b e a n d animal studies, c a t h o m y c i n c o m b a t t e d gram positive b a c t e r i a particularly staphylococci causi n g abscesses, blood s t r e a m infections, a n d osteomyelitis; against bacteria causi n g p n e u m o n i a a n d e a r a n d t h r o a t inf e c t i o n s ; a g a i n s t Proteus vulgaris, w h i c h c a u s e s serious u r i n a r y t r a c t i n f e c t i o n s ; a n d against whooping cough. Favor-
a b l e results h a v e b e e n o b t a i n e d in p r e l i m i n a r y clinical t e s t s . A p r e v i o u s l y u n k n o w n s p e c i e s . Streptomyces sphéroïdes, produces cathomyc i n . I t is a c i d i c , f o r m s v a r i o u s salts, a n d is optically a c t i v e . T w o c r y s t a l line forms h a v e b e e n o b t a i n e d . • S y n e r g i s t i n is a n e w Pfizer a n t i b i o t i c c o n t a i n i n g t w o a c t i v e fractions A a n d Β w h i c h a p p e a r to h a v e s y n e r gistic a c t i o n . I t is effective a g a i n s t gram positive b a c t e r i a , particularly those resistant to o t h e r antibiotics. It p r o v i d e d significant p r o t e c t i o n a g a i n s t e x p e r i m e n t a l i n f e c t i o n s in w h i t e m i c e , w h e n a d m i n i s t e r e d orally or b y injec tion. A strain of Streptomyces resembling S. olivaceous elaborates the two parts; t h e y a r e r e c o v e r a b l e t o g e t h e r from fer m e n t a t i o n filtrates b y solvent e x t r a c t i o n . T h e y c a n b e s e p a r a t e d b y differ e n t i a l solvent solubility, p u r i f i e d b y countercurrent distribution, a n d crys tallized. S y n e r g i s t i n A is a n e u t r a l c o m p o u n d CarJrlaoNaOe, w h i l e Β is acidic, C^HeaNeOw.
fife.' 1ψ Λ Oik
^
B a c t e r i a r e s i s t a n t t o a n t i b i o t i c s a r e t h e t a r g e t of M e r c k ' s n e w a n t i b i o t i c , c a t h o m y c i n , a n d t h e c h e m i s t s w h o i s o l a t e d it i n c r y s t a l l i n e f o r m : Fern. P. Rathe ( l e f t ) , K a r l F o l k e r s , a n d E d w a r d A, K a c z k a . C a t h o m y c i n w a s o n e of s e v e r a l a n t i b i o t i c s discussed b e f o r e t h e t h i r d a n n u a l Symposium o n Antibiotics 4916
C&EN
NOV.
14.
1955
• T h i o s t r e p t o n h a s b e e n isloated b y S q u i b b scientists from a f e r m e n t a t i o n b r o t h p r e p a r e d w i t h a n unclassified s p e c i e s of Streptomyces. I t is a c t i v e primarily against t h e g r a m positive group, particularly staphylococci which h a v e a t e n d e n c y to b u i l d u p r e s i s t a n c e t o o t h e r a n t i b i o t i c s s u c h as p e n i c i l l i n , erythromycin, carbomycin tetracycline, streptomycin, neomycin, bacitracin, gramicidin, and Chloromycetin. It a p pears t o h a v e clinical promise. P e p t i d e linkages are indicated, b u t p h y s i c a l p r o p e r t i e s s e r v e t o differenti ate it from other k n o w n polypeptide antibiotics. r Vancomycin,
produced by
a
new
s p e c i e s , Streptomyces orientalis, is a c tive a g a i n s t a v a r i e t y of g r a m p o s i t i v e organism a n d spirochetes, according to Lilly r e s e a r c h l a b s . I t s h o w s e x t r e m e l y l o w t o x i c i t y in s t u d i e s i n t i s s u e c u l t u r e a n d a n i m a l s ; p r e l i m i n a r y d a t a s h o w it is c l i n i c a l l y effective a g a i n s t s e v e r a l d i s e a s e s . I n vitro, it is c h a r a c t e r i z e d b y l a c k of d e v e l o p m e n t of r e s i s t a n c e i n s t r a i n s of Micrococcus pyogenes var. aureus. • Albamycin has p r o v e d effective a g a i n s t a w i d e v a r i e t y of infections in p r e l i m i n a r y clinical t r i a l s , says U p j o h n . T h e y i n c l u d e b a c t e r i a l i n f e c t i o n in t h e skin, l u n g s , b o n e , u r i n a r y t r a c t , a n d b l o o d s t r e a m . T h u s far, it h a s s h o w n n o t o x i c effects e v e n after t h r e e w e e k s of a d m i n i s t r a t i o n in l a r g e doses. Of " m e d i u m m o l e c u l a r w e i g h t , " it is a heterocyclic compound a n d promises to s h o w s o m e n e w t y p e s of c h e m i c a l s t r u c t u r e . I t is p r o d u c e d b y Streptomyces nivens. Upjohn points to two unique and c l i n i c a l l y significant f e a t u r e s : it h a s s h e w n n o cross r é s i s t a n t e , it gives t h e highest blood levels ever experienced with a n y antibiotic. • R o v a m y c i n , t e s t e d in Hospital B e a u j o n , C l i c h y , F r a n c e , is a b r o a d spectrum antibiotic, namely active against gram positive bacteria and Neisseria. V e r y g o o d results h a v e b e e n o b t a i n e d in t r e a t m e n t of p n e u m o p a t h i e s , e s p e c i a l l y in^ p n e u m o n i a of o l d a g e . It is v e r y effective a g a i n s t a c u t e t o n s i l litis, i n f e c t i o u s e n d o c a r d i t i s , a n d p r i n c i p a l l y in s t a p h y l o c o c c a l c o n d i t i o n s . T h e F r e n c h g r o u p is p r e d i c t i n g a n e w d e v e l o p m e n t i n t r e a t m e n t of s t a p h y l o coccal conditions. • Amphotericin A and Β show prom ise of effective a c t i o n a g a i n s t a w i d e r v a r i e t y of infectious f u n g i t h a n a n y of t h e a n t i f u n g a l a g e n t s n o w a v a i l a b l e for u s e in m a n , a c c o r d i n g t o S q u i b b , which recently marketed nystatin (C&EN, Nov. 7 , page 4 7 9 6 ) . The two were isolated from a hitherto unidenti fied m o l d of Streptomyces. I n experimental infections in m i c e simulating various serious fungal infec-
Advances in Applied Radiation
USED TO PRODUCE IT DEVELOPMENTS in t h e FIELD OF APPLIED RADIATION ENERGY, its APPLICATIONS and the APPARATUS USE
Bring your questions a b o u t radiation-energy applications to Booth 3 1 9 — I n t e r n a t i o n a l Atomic Exposition C l e v e l a n d — D e c e m b e r ΊΟ-Ί 6 Gulf Oil to Install Powerful Atom Smasher
Gulf Oii Corporation has an nounced plans for a nuclear science laboratory to be located at the com pany's research center in Harmarville, Pennsylvania. Principal unit in the laboratory will be a giant three-mil lion-volt atom smasher which is being built by High Voltage Engineering Corporation, Cambridge, Massachu setts. This V a n de GraafF Particle Accelerator, capable of producing virtually all the fundamental forms of radiation in powerful streams of elec trons, x-rays, positive ions, or neu trons, will be installed approximately September 1, 1956. Gulf scientists will use the accel erator to study the effects of radiation on a wide range of petroleum and petrochemical processes, a s well as for improved analytical techniques and the development of new catalytic agents — exjalpring every possible application of nuclear energy in the manufacture of petroleum and petro chemical products. Dr. Blaine B. Wescott, Gulf Vice-President in Charge of Research, expressed the hope that the new accelerator will solve many mysteries of petroleum refining and production still confronting scientists. "We intend," Dr. Wescott pointed out, "to find out if radiation can be
used to improve performance characteristics of petroleum products. T o day we rely largely o n heat to change or rearrange the molecular structure of crude oil in order that we may produce o u r petroleum products. N o w we need to find out if, through n u clear energy, important improvements can be made in conventional refining and petrochemical processes. If this should prove feasible, it could lead t o the development of totally new a n d different products as well as to more efficient refining operations whereby we can achieve absolute maximum usage from a barrel of crude." Radiation-Sterilized Plastic Tubing Introduced
The first electron-sterilized plastic tubing available commercially is now being marketed by the Clay-Adams Company, Inc., New York manufacturer of medical and surgical equipment and supplies. The new product is marketed under the Clay-Adams registered trade name of "Intramedic" Polyethylene Tubing. Available in convenient lengths, the tubing is packaged in sterile, sealed, plastic envelopes. T h e whole package is irradiated in one operation by passing it through a beam of electrons emitted by H I G H VOLTAGE'S 2-million-electron-volt V a n
de Graaff accelerator. Complete sterility within the envelope is achieved within a few seconds. H I G H VOLTAGE
fà&Z£B
performed the experimental testing irradiations for Clay-Adams in its 2= million-volt radiation facility at its plant in Cambridge. The sterile tubing is available in diameters of from . 0 3 8 " to .075". The irradiation of this plastic tubing by H I G H VOLTAGE further estab-
the
proton
lishes that complete sterilization can be accomplished economically using a Van de Graaff as a radiation source.
Six-MeV Accelerator for France
The French Ministry of Education has ordered a six-million-volt Van d e Graaff positive ion accelerator from HIGH
VOLTAGE.
Scheduled
for
in-
stallation in 1957, at the Institut de Recherche Nucléaires in Strasbourg, the accelerator will be used under the direction of Professor S. Gorodetsky to study the excited levels of nuclei.
IS
versatile
nïjGMVblTAGE Γ ^ 7 U N I V ER SI TV R O A D
G ΑΊΑ Β R I D G Ε 3 8 , M AS S A C Η U S
t h e r m a l neutrons/
NOV.
14,
1955
C&EN
4917
RESEARCH
tions in man, they w e r e effective when administered b y mouth. I n addition, skin infections such as ringworm re spond to amphotericin ointment. ί Antibiotic # 1 9 6 8 from N e p e r a Chemical shows markedly beneficial effect against various fungus diseases in mice. Intravenous toxicity for mice is of same order as b r o a d spectrum anti biotics. Preliminary findings suggest it warrants further investigation as a potential chemotherapeutic agent for systemic mycoses in man. • Eulicin inhibits a number of higher fungi at minute concentrations, ac cording to Merck. Obtained from cul ture filtrates of a species of Streptomyces, it is not a member of the group of polyenes like nystatin which have demonstrated antifungal activity.
Needed : A Better Seal
g l a s s ni CùiiLiiiuOU.5 riciùpfeîïê
N e w types o f construction materials push n e e d for more s a t i s f a c t o r y glazing a n d caulking compounds WASHINGTON, D. C.-Widening popularity of new types of construction is having a strong impact on t h e "use of glazing and caulking compounds. W h e n the boom in construction got under way with the end of World W a r II, it brought w i t h it changes in architectural tastes a n d methods: • Aluminum sash came into wide use. • Larger lights of glass and insulated glass windows were commonly desired. • Metal curtain wall construction be came accepted. Use of such materials, however, carried in its wake a need for engineer ing them so as to prevent leakage between glass and sash or between the joints of metal panels, yet allow for expansion and contraction or move ment caused b y temperature changes or wind pressure. Conventional glazing and caulking compounds have not filled the rigid requirements set up b y users of these new types of materials, who laid their problems before manufac turers during a forum session at the annual convention of the National Paint, Varnish & Lacquer Association. Typical of t h e problems that builders m a y run into, says J. P . Jansson of the Aluminum Window Manufacturers Association is t h e experience a t Lever House, built in New York about five years ago. T h e glazing compound used for the windows of the building was found to b e drying out, resulting in loose and broken glass. It became 4918
C&EN
NOV.
! 4,
necessary to do a. pointing j o b o n all the glass in t h e building, using a Thiokol synthetic rubber c o m p o u n d . This material, although it has per formed satisfactorily, is relatively ex pensive t o use, roust b e m i x e d o n t h e job, is difficult t o store, a n d must b e applied with a gum under pressure. T h e n e w Alcoa building in Pitts burgh, described Dy Alcoa's H . F. John son, presents o n e solution t o t h e caulking problem in curtain wall con struction. T h e wall panels w e r e d e signed s o that they did n o t require caulking materials t o p r e v e n t water from leaking between thern. I n still another case, a lajcge auto mobile manufacturer, troubled with leakage of w a t e r a r o u n d the fixed windows of a n e w building a n d finding that several conventional glazing com pounds were completely unsatisfactory, eliminated such materials b y setting t h e
1955
pounds tested by L-O-F become rockhard in a matter of weeks or m o n t h s after application; although a few have been found to retain some plasticity after prolonged exposure t o weather, not one low or moderately priced compound is entirely satisfactory. Thiokolbase mastics seem to b e best, he adds, providing a good water seal between glass and sash and a good cushion for the glass, b u t t h e y are relatively expensive and difficult to use. I n the face of the rigid demands of newly developing markets, NPVLA's forum seems agreed: W h a t is n e e d e d is more cooperative research, development, and promotional efforts aimed at profiting from the needs of t h e construction industry for better sealing materials.
SéeLiûiiS.
Because improper handling and mixing of glazing compounds may lead to poor results, some manufacturers of aluminum windows n o longer recommend their use b u t instead a r e preglazing their windows at the factory using neoprene or vinyl glazing beads. None of these answers to the problem, however, i s as economic or as practical as is desired. W h a t is n e e d e d is a sealing material which can b e a p plied and will stand u p without hardening or shrinkage over the wide range of temperatures t o w h i c h building exteriors a r e exposed, which is neither too thick nor too thin a n d can b>e applied without doctoring i n the field, and which will not bleed or crack—all this for a price of about 5 cents a p o u n d . According to Libby-Owens-FOrd's Otto Wenzler, most commercial glazing com-
Oxygen-containing comp o u n d in organic electrical insulating m a t e r i a l prevents carbonization ORGANIC
ELECTKICAL
INSULATING
MATERIALS often fail because tbey tend to carbonize and form a conducting track o n exposure to electric arcing conditions. Although m a n y improved insulation materials h a v e been developed, very little had b e e n done to improve this fundamental weakness of organic insulators until R. S. Norman, R. A. Pfuntner, and A. A. Kessel at General Electric succeeded in building into the organic material a n oxidation mechanism to prevent carbonization. At t h e fall general meeting of the
Semimicro Dilution Viscometer Polymer chemists with only 1 ml. of solution c a n still determine molecular weights with this accurate semimicro dilution viscometer developed b y Victor E. H a r t , National Bureau of Standards. It is said to differ from other semimicro viscometers in t h a t it is suitable for dilutions and reruns of a solution. It also eliminates errors from solvent evaporation. Viscosity i s measured in terms of the time required for a given quantity of solution t o flow through a triple-bend capillary.
